The major objective of our studies is to characterize cell surface structures on T lymphocytes which, in addition to the antigen- specific receptor (TCR), play critical roles both in vivo and in vitro in the process of lymphocyte activation. The TCR as well as other cell surface antigens of Thy-1+ dendritic epidermal T cells (DETC), a unique population of cells comprising 1-2% of murine epidermis, have been extensively characterized. DETC bear exclusively gamma delta-TCR; a combination of biochemical and molecular approaches has shown that both the TCR gamma-chain and the TCR delta-chain expressed by this population of cells exhibits considerable diversity. A panel of monoclonal antibodies (mAbs) has been generated against DETC. One mAb recognizes a cell surface disulfide linked dimer of 85 kD under non-reducing conditions. In the presence of phorbol esters, this mAb is a potent stimulator of T cell activation. Its biochemical and functional properties suggest that this mAb identifies the murine homologue of the human CD28 antigen. A second group of mAbs identify members of the Integrin Superfamily of Cell Adhesion Molecules (I-SCAM). These mAbs specifically inhibit the binding of DETC to a number of extracellular matrix proteins. We have also continued our studies of the Thy-1 and Ly-6 antigens which are coupled to the cell membrane via a phosphatidylinositol (PI) linkage. We have obtained evidence for additional PI-linked proteins which may play important roles in cell-cell interaction. An Ly-6 linked gene has been cloned and shown by transfection studies to be Ly-6A.2. Lastly, we have shown that T lymphocytes can be activated in vivo by allogeneic cells in the presence of the immunosuppressive drug, Cyclosporin A (Cy A) and that this activation process is independent of any of the known Interleukins.